A small randomized trial posted as a preprint and indexed by Europe PMC reports that a combination of the investigational peptide NVG-291 and thymosin beta-4 was associated with larger motor and walking gains than placebo over 12 months in people with complete spinal cord injury.

NVG-291 targets PTPσ, a receptor the authors describe as relieving proteoglycan-mediated inhibition of axonal growth. Thymosin beta-4 (TB-4) is credited with cytoprotective and anti-inflammatory actions, and the stated rationale is that the two mechanisms are complementary and may improve the response to rehabilitation.

How the trial was run

The single-center, double-blind study enrolled 30 participants with complete (AIS A) injuries at the NuRaX Center in partnership with Ege Hospital in Baku, Azerbaijan, randomized 1:1 to the combination protocol or saline placebo. Dosing was NVG-291 2.5 mg plus TB-4 1.5 mg subcutaneously every 14 days for 12 months, with a single 3.5 mg paraspinal NVG-291 dose at T11 to T12.

Both arms received the same conservative rehabilitation program, with no stimulation or robotic equipment, and placebo injections were matched for volume, route and timing. Assessments were independently re-screened by blinded external consultants, which is more than most small single-site studies bother with.

Key results

Mean lower extremity motor score rose 7.6 points in the combination group against 0.6 points on placebo, a between-group difference of 7.0 points (95% CI, 4.8 to 9.2). Standing duration increased by 4.01 minutes more in the treated group (95% CI, 2.37 to 5.65).

At 12 months, 13 of 15 combination participants (86.7%) completed 100 meters with a walker, without orthoses or physical assistance, compared with 1 of 15 on placebo (6.7%). No adverse events or injection-site reactions were documented.

What did not change

No participant converted to a different AIS grade, and the authors report no change in bladder or bowel function in either arm. In a population defined by complete injury, that gap between measured walking performance and unchanged neurological classification is the most interesting unanswered question in the paper.

Limitations

This is a preprint, so it has not been through peer review. It is also a single center with 30 participants total, 15 per arm, and the authors note the trial was investigator-initiated and call for larger, prospectively registered randomized trials.

Where the evidence stands

The effect sizes reported here are unusually large for this population, which is a reason to take the result seriously and a reason to want it replicated elsewhere. Until an independent, registered trial runs, this is one unreviewed study of 30 people.